Trial Outcomes & Findings for Effects of Intravenous GC4419 on the Incidence and Severity of Esophagitis Due to Chemoradiotherapy for Lung Cancer (NCT NCT04225026)

Last Updated: 2023-03-23

Results Overview

Those subjects in the primary efficacy population that experience acute radiation esophagitis (Grade \>/=2; NCI CTCAE version 5) through the end of chemoradiotherapy for NSCLC or SCLC when treated with avasopasem. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization Grade 4: life-threatening consequences; urgent operative intervention indicated Grade 5: death

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

39 participants

Primary outcome timeframe

From the first radiation therapy fraction through the end of the study treatment period, which is estimated to be 6 weeks.

Results posted on

2023-03-23

Participant Flow

Participant milestones

Participant milestones
Measure	GC4419 GC4419: 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Overall Study STARTED	39
Overall Study Primary Efficacy Population	35
Overall Study Per Protocol Population	29
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Reasons for withdrawal
Measure	GC4419 GC4419: 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Overall Study Withdrawal by Subject	4
Overall Study Adverse Event	1
Overall Study Other	1
Overall Study Death	11
Overall Study Study Terminated Early By Sponsor	7

Baseline Characteristics

There were 39 subjects enrolled to the study but only 35 subjects were included in the primary efficacy analysis population based on the primary efficacy population definition.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GC4419 n=39 Participants GC4419: 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Age, Continuous	65.1 years STANDARD_DEVIATION 9.34 • n=5 Participants • There were 39 subjects enrolled to the study but only 35 subjects were included in the primary efficacy analysis population based on the primary efficacy population definition.
Sex: Female, Male Female	17 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Sex: Female, Male Male	22 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Race (NIH/OMB) Asian	1 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Race (NIH/OMB) White	36 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Region of Enrollment United States	39 participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Type of Lung Cancer NSCLC	32 participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.
Type of Lung Cancer SCLC	7 participants n=5 Participants • Their were 39 subjects enrolled to the study but only 35 subjects were included in the analysis population based on the primary efficacy population definition.

PRIMARY outcome

Timeframe: From the first radiation therapy fraction through the end of the study treatment period, which is estimated to be 6 weeks.

Population: Primary Efficacy Population included all subjects who received at lease 1 dose of GC4419 (avasopasem manganese) and either completed their radiation therapy or discontinued their radiation therapy early but were known to have had acute radiation esophagitis.

Outcome measures

Outcome measures
Measure	GC4419 (Avasopasem Manganese) n=32 Participants GC4419 (avasopasem manganese): 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. Condition Not Present	7 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. Grade 1	6 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. Grade 2	17 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. Grade 3	2 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. Grade 4	0 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through the End of Chemoradiotherapy for Non-Small Cell Lung (NSCLC) or Small Cell Lung Cancer (SCLC) When Avasopasem Was Added. Grade 5	0 Participants

SECONDARY outcome

Timeframe: From the first radiation therapy fraction through 4 weeks after the completion of chemoradiotherapy, which is estimated to be 10 weeks

Those subjects in the in the primary efficacy population that experience Grade \>/= 2 (NCI CTCAE version 5) acute radiation esophagitis through 4 weeks after completion of chemoradiotherapy for NSCLC or SCLC when treated with avasopasem. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization Grade 4: life-threatening consequences; urgent operative intervention indicated Grade 5: death

Outcome measures

Outcome measures
Measure	GC4419 (Avasopasem Manganese) n=34 Participants GC4419 (avasopasem manganese): 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy Grade 1	4 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy Grade 2	10 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy Grade 3	1 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy Grade 4	0 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy Grade 5	0 Participants
Number of Subjects With of Acute Radiation Esophagitis (Defined as Grade >/= 2; NCI CTCAE Version 5) Through 4 Weeks After Completion of Chemoradiotherapy Condition Not Present	19 Participants

SECONDARY outcome

Timeframe: From the first radiation therapy fraction through the completion of chemoradiotherapy, which is estimated to be 6 weeks.

Population: Per protocol population defined as those subjects completing chemoradiation therapy and at least 5 weeks of GC4419

Those subjects in the per protocol population that experienced Grade 3-4 acute radiation esophagitis through the completion of chemoradiotherapy. NCI CTCAE Grading: Grade 1: asymptomatic; clinical or diagnostic observations only; intervention not indicated; Grade 2: symptomatic; altered eating/swallowing; oral supplements indicated; Grade 3: severely altered eating/swallowing; tube feeding, total parental nutrition (TPN) or hospitalization; Grade 4: life-threatening consequences; urgent operative intervention indicated; Grade 5: Death.

Outcome measures

Outcome measures
Measure	GC4419 (Avasopasem Manganese) n=29 Participants GC4419 (avasopasem manganese): 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. Condition Not Present	7 Participants
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. Grade 1	6 Participants
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. Grade 2	13 Participants
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. Grade 3	1 Participants
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. Grade 4	0 Participants
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. Grade 5	0 Participants
Number of Subjects With Acute Severe Radiation Esophagitis (Defined as Grade 3-4; NCI CTCAE Version 5) Through Completion of Chemoradiotherapy. Assessment Not Performed	2 Participants

Adverse Events

GC4419

Serious events: 15 serious events

Other events: 39 other events

Deaths: 11 deaths

Serious adverse events

Serious adverse events
Measure	GC4419 n=39 participants at risk GC4419: 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	7.7% 3/39 • Number of events 3 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Respiratory, thoracic and mediastinal disorders Hypoxia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Respiratory, thoracic and mediastinal disorders Respiratory Failure	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Dysphagia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Haematemesis	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Nausea	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Odynophagia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Vomiting	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Metabolism and nutrition disorders Dehydration	5.1% 2/39 • Number of events 2 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Metabolism and nutrition disorders Adult Failure to Thrive	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Metabolism and nutrition disorders Hypomagnesaemia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Infections and infestations Corona Virus Infection	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Infections and infestations Influenza	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Infections and infestations Lung Infection	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Infections and infestations Pneumonia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Infections and infestations Sepsis	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Blood and lymphatic system disorders Anemia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Blood and lymphatic system disorders Pancytopenia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Blood and lymphatic system disorders Thrombocytopenia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
General disorders Non Cardiac Chest Pain	5.1% 2/39 • Number of events 2 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Injury, poisoning and procedural complications Femur Fracture	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Injury, poisoning and procedural complications Vascular Access Complication	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Vascular disorders Embolism	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Vascular disorders Hypotension	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Cardiac disorders Atrial Tachycardia	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Musculoskeletal and connective tissue disorders Pain in Extremity	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Psychiatric disorders Confusional State	2.6% 1/39 • Number of events 1 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).

Other adverse events

Other adverse events
Measure	GC4419 n=39 participants at risk GC4419: 90 mg, by 60-minute IV infusion, prior to each fraction of RT
Nervous system disorders Paraesthesia	20.5% 8/39 • Number of events 84 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Nausea	56.4% 22/39 • Number of events 60 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Dysphagia	51.3% 20/39 • Number of events 53 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	28.2% 11/39 • Number of events 33 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
General disorders Fatigue	61.5% 24/39 • Number of events 32 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).
Gastrointestinal disorders Vomiting	38.5% 15/39 • Number of events 30 • Adverse events were collected from baseline (Study Day 1) until 30 days post the last day of radiation therapy (approximately 10 weeks).

Additional Information

Judy Schnyder, Sr. Vice President, Clinical Operations

Galera Therapeutics

Phone: 484-870-9625

Email: [email protected]

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